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However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60\u2009months. We analyzed location\u2010specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all\u2010cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet\u2010derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR]\u00a0=\u00a01.02, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR\u00a0=\u00a01.01, 95% confidence interval [CI]\u00a0=\u00a01.00\u20131.03 and HR\u00a0=\u00a01.05, 95% CI\u00a0=\u00a01.00\u20131.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence\u2010based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.<\/jats:p>","DOI":"10.1002\/cjp2.218","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T18:47:25Z","timestamp":1620326845000},"page":"482-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["High tumor cell platelet\u2010derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5381-4188","authenticated-orcid":false,"given":"Hely","family":"Ollila","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE) University of Helsinki  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of 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